Steve Davis: Yeah. I think, Charles, our standard response when we are in registration is not to comment on back and forth we have with the agency. But I just simply say that, they have been very engaged. We are eager to get our PDUFA day, but we don’t comment on things otherwise. I — just one important contextual point, I just want to mention in terms of diarrhea. I know we have said it before, it’s a really important point, though. Rett patients on average have about 80% of them have significant constipation and it can get quite severe. It can lead to impaction, hospitalization. They have even a few reported cases of death due to sepsis associated with constipation and infection. So this is very top of mind in the right community with physicians, as well as caregivers.
And so in some respects, the diarrhea effect that we see with trofinetide can be somewhat of a trade-off. And you also have a situation where almost all of these Rett patients were diaper type garments sertraline. And so just some additional context around that, and as Kathie mentioned, a lot of diarrhea management mitigation regimen steps that we took late in or that we developed late in the LAVENDER study that time, significant majority of patients in LILAC had already been completed that 40-week program as well. So we are very eager to get to the finish line here. And as Brendan described earlier, we have a lot of resources that will put — that will bring to bear to help families manage the tolerability of trofinetide, which we think is significantly outweighed by the significant benefits that we see, which we see continuing sustained and continuing to grow through the LILAC study.
Charles Duncan: Thanks, Steve and Kathie.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Neena Bitritto-Garg from Citi.
Neena Bitritto-Garg: Hey, guys. Thanks for taking my question. Just a follow-up on the last question on the impact of diarrhea and discontinuation. Just curious if you can comment on what happened when you did implement the diarrhea management program in the LILAC open-label extension study. Did you see that patients who were maybe earlier in the OLE did have a lower discontinuation rate? I am just trying to contextualize how to think about the impact of the diarrhea management on the discontinuation rate? Thanks.
Kathie Bishop: Yeah. Thanks for the question.
Steve Davis: Kathie, go ahead.
Kathie Bishop: So as we implemented the diarrhea management plan, which as Steve mentioned, it’s really important to keep into context that 80% of these patients have constipation, which can be very severe. The first step in the plan is to stop taking your anti-constipation medications and many of these patients are on two or three of those and then to implement anti-diarrhea over-the-counter measures such as increase in fiber in the diet and over-the-counter loperamide. So as that plan rolled out and then became implemented by the caregivers and the physicians in the trial, we certainly hear feedback that those steps are helping to control the diarrhea and later on in the trial keep patients trofinetide. I should also add, as we are talking about diarrhea, remember that the diarrhea is almost all mild or moderate in nature and it’s not a safety concern.
It does not lead to dehydration, does not lead to weight loss, does not lead to hospitalization. So this is really a management issue and through the trials and working with some of the study nurses and clinicians, I think, we put in place steps to help parents better manage it and that’s what we intend to do as we move towards hopeful commercialization.
Neena Bitritto-Garg: Got it. Thank you.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Yatin Suneja from Guggenheim Partners.
